Oxidative modification enhances the immunostimulatory effects of extracellular mitochondrial DNA on plasmacytoid dendritic cells, Free Radical Biology and Medicine, http://dx.doi.org/10.1016/j. freeradbiomed. 2014.09.028 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.www.elsevier.com/locate/freeradbiomed Abbreviations: 7-AAD, 7-aminoactinomycin-D; 8-oxoG, 8-oxo-7,8-dihydroguanine; 8-oxodG, 8-oxo-7,8-dihydro-2'- well as increased TNF-Į and IL-8 production from the cells. These effects were more apparent when pDCs were exposed to oxidatively modified mtDNA. Neither native nor oxidized mtDNA molecules were able to induce interferon (IFN)-Į secretion from pDCs unless they formed a complex with human cathelicidin LL-37, an antimicrobial peptide.Interestingly, simultaneous administration of a Toll-like receptor (TLR)9 antagonist abrogated the effects of both native and oxidized mtDNAs on human pDCs. In a murine model, oxidized mtDNA also proved a more potent activator of pDCs compared to the native form, except for induction of IFN-Į production. Collectively, we demonstrate here for the first time that elevated levels of 8-oxoG bases in the extracellular mtDNA induced by oxidative stress increase the immunostimulatory capacity of mtDNA on pDCs. 3 HighlightsWe compared the immunostimulatory capacity of native and oxidized mtDNA on pDCs.8-Oxoguanin-containing mtDNA has a greater capacity to activate primary human pDCs.In vivo, oxidized mtDNA also proved a more potent activator of pDC than native mtDNA.

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BACKGROUND: Flap hypoperfusion or ischemia-reperfusion (I/R) may occur during preparation-transposition procedures and by postoperative thrombotic complications. Behind the microcirculatory disturbances micro-rheological alterations are also supposed. OBJECTIVE:We aimed to investigate the groin flap I/R with following-up micro-rheological parameters.METHODS: Anesthetized rats were subjected to Control or I/R groups. Groin flaps were prepared bilaterally, pedicled on the superficial epigastric vessels. In Control group the flaps were re-sutured after one hour, while in I/R group microvascular clips were applied on the pedicles for 60 minutes, then the flaps were repositioned. Besides daily wound control, before the operation and on the 1st, 3rd, 5th, 7th and 14th postoperative days blood samples were collected for testing red blood cell (RBC) deformability (rotational ektacytometry) and aggregation (light-transmission aggregometry). RESULTS:RBC deformability significantly worsened by the 3rd-7th postoperative day in I/R group. RBC aggregation enhanced significantly by the 1st day, in I/R group it remained elevated on the 3rd day as well. In a complicated case with unilateral flap necrosis, RBC deformability and aggregation worsening was outlined from its group (base, 1st, 3rd day). CONCLUSION:Wound healing affected micro-rheological parameters in the early postoperative period. Flap I/R exacerbated the alterations. The parameters markedly worsened in case of flap necrosis.

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Abstract.Rheopheresis is an extracorporal selective double-filtration procedure. In the first part of the treatment the blood 8 is passes through the plasma filter, which separates blood cells from the plasma. Then the plasma flow to a second filter

Forasmuch in the circulation both elongation by shear stress and filtration occur, these various erythrocyte deformability testing methods together may describe better the alterations. Considering the possible complications related to functional asplenic-hyposplenic conditions, individual analysis of cases is highly important.

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